A Practical Guide to Lesion Symptom Mapping

The purpose of this guide is to provide a detailed overview of everything researchers need to think about and do when conducting lesion symptom mapping (LSM) analysis. This guide includes step-by-step instructions for data collection, lesion delineation, lesion normalisation, LSM, secondary analyses, results interpretation, and write-up. All original scripts and analysis tools referenced in this guide are openly availible on the Open Science Framework.

Brain Substrates for Distinct Spatial Processing Components Contributing to Hemineglect in Humans

Several cortical and sub-cortical regions in the right hemisphere, particularly in the parietal and frontal lobes, but also in the temporal lobe and thalamus, are part of neural networks critically implicated in spatial and attentional functions. Damage to different sites within these networks can cause hemispatial neglect. The aim of this study was to identify the neural substrates of different spatial processing components that are known to contribute to neglect symptoms. Firstly, three different spatial tasks (visual search, bisection, and visual memory) were tested in 26 healthy controls. The fMRI results showed a differential activation of regions in the parietal and frontal lobes during bisection and visual search, respectively. Secondly, fMRI was used in 27 patients with focal right brain damage. Voxel-based lesion–symptom mapping was used to determine the relationships between specific sites of damage and the severity of deficits in these three spatial tasks. In the patients, we confirmed a critical role of the right lateral parietal cortex in bisection, but lesions in the frontal and temporal lobes were critical for visual search. These data support the existence of distinct components in spatial attentional processes that might be damaged to different degrees in neglect patients.

Lesion-symptom mapping with NIHSS sub-scores in ischemic stroke patients

BackgroundLesion-symptom mapping (LSM) is a statistical technique to investigate the population-specific relationship between structural integrity and post-stroke clinical outcome. In clinical practice, patients are commonly evaluated using the National Institutes of Health Stroke Scale (NIHSS), an 11-domain clinical score to quantitate neurological deficits due to stroke. So far, LSM studies have mostly used the total NIHSS score for analysis, which might not uncover subtle structure–function relationships associated with the specific sub-domains of the NIHSS evaluation. Thus, the aim of this work was to investigate the feasibility to perform LSM analyses with sub-score information to reveal category-specific structure–function relationships that a total score may not reveal.MethodsEmploying a multivariate technique, LSM analyses were conducted using a sample of 180 patients with NIHSS assessment at 48-hour post-stroke from the ESCAPE trial. The NIHSS domains were grouped into six categories using two schemes. LSM was conducted for each category of the two groupings and the total NIHSS score.ResultsSub-score LSMs not only identify most of the brain regions that are identified as critical by the total NIHSS score but also reveal additional brain regions critical to each function category of the NIHSS assessment without requiring extensive, specialised assessments.ConclusionThese findings show that widely available sub-scores of clinical outcome assessments can be used to investigate more specific structure–function relationships, which may improve predictive modelling of stroke outcomes in the context of modern clinical stroke assessments and neuroimaging.Trial registration numberNCT01778335.

An evaluation of language in brain tumour patients using a new cognitive-motivated testing protocol

<p>In patients undergoing tumour resection surgery, assessment of language is vital, given its crucial role in everyday social functioning. However, despite the unique neuropathological mechanisms in tumours, current literature presents variable results regarding language capabilities in this population. In this thesis we have developed a new neuropsychological test battery, the Brief Language Assessment for Surgical Tumours (BLAST), to specifically evaluate language in brain tumour patients. The BLAST adopts a core skills approach, which identifies and examines 11 core cognitive skills that have been derived based on current cognitive and psycholinguistic theories, and are required for everyday language processing. In this study, we administered the BLAST to a cohort of 40 undifferentiated tumour surgery patients, both pre and postoperatively. Also tested were 60 healthy controls categorised into three age groups (18-29, 30-50 and 51+years). We examined various aspects of overall test performance in order to evaluate: 1) the overall sensitivity of the test battery at detecting abnormalities in this population; 2) selectivity: the relative incidence of impairments across the various subtests; and 3) their sensitivity to change following surgery. We also explored the effects of lesion localisation and other lesion characteristics (malignancy, oedema and volume) on test performance. Following this, we then used participants' test performance to create operationalised measures of our 11 core cognitive skills, and evaluated these measures in a similar way to the basic test scores. Finally, we used Voxel-Based Lesion Symptom Mapping to determine the specific anatomical predictors for each core cognitive skill score. When investigating overall task performance, we found that 94% of preoperative patients and 90% of postoperative patients were impaired in at least one task within the BLAST. Also, 65% and 68% of patients had impaired scores on at least one core skill preoperatively and postoperatively respectively. It was also found that the core skills measures were effective at discriminating amongst different neurological profiles. Specifically, patients with a left posterior tumour had significantly lower scores than other groups on measures of accessing semantic knowledge, lexical selection and phonological encoding, either pre or postoperatively, or both. Conversely, patients with a left frontal tumour had significantly lower scores on measures of articulatory motor planning and verb retrieval. Our Voxel-Lesion-Symptom-Mapping analysis corroborated these findings. Lesions within the left superior temporal lobe significantly predicted lows scores in accessing semantic knowledge, lexical selection and phonological encoding. Conversely, lesions within the left inferior, as well as the superior posterior frontal lobe, significantly predicted low scores on goal-driven response selection, articulatory-motor planning and verb retrieval. We conclude that a core skills approach may be a more effective means of assessing language in tumour populations than more conventional tools that emphasise overall task performance. Such derived measures are sensitive to impairments in this population, and are less likely to be confounded by nonlinguistic impairments that can impact significantly on overall task scores. They may also be useful in guiding postoperative rehabilitation. Further, the scores derived here are associated with quite specific neural substrates, making them potentially useful in guiding surgery and reducing postoperative linguistic deficits. Finally, we conclude that the investigation of tumour populations can also provide unique theoretical insights into language processing and its neural underpinnings in its own right.</p>

An evaluation of language in brain tumour patients using a new cognitive-motivated testing protocol

<p>In patients undergoing tumour resection surgery, assessment of language is vital, given its crucial role in everyday social functioning. However, despite the unique neuropathological mechanisms in tumours, current literature presents variable results regarding language capabilities in this population. In this thesis we have developed a new neuropsychological test battery, the Brief Language Assessment for Surgical Tumours (BLAST), to specifically evaluate language in brain tumour patients. The BLAST adopts a core skills approach, which identifies and examines 11 core cognitive skills that have been derived based on current cognitive and psycholinguistic theories, and are required for everyday language processing. In this study, we administered the BLAST to a cohort of 40 undifferentiated tumour surgery patients, both pre and postoperatively. Also tested were 60 healthy controls categorised into three age groups (18-29, 30-50 and 51+years). We examined various aspects of overall test performance in order to evaluate: 1) the overall sensitivity of the test battery at detecting abnormalities in this population; 2) selectivity: the relative incidence of impairments across the various subtests; and 3) their sensitivity to change following surgery. We also explored the effects of lesion localisation and other lesion characteristics (malignancy, oedema and volume) on test performance. Following this, we then used participants' test performance to create operationalised measures of our 11 core cognitive skills, and evaluated these measures in a similar way to the basic test scores. Finally, we used Voxel-Based Lesion Symptom Mapping to determine the specific anatomical predictors for each core cognitive skill score. When investigating overall task performance, we found that 94% of preoperative patients and 90% of postoperative patients were impaired in at least one task within the BLAST. Also, 65% and 68% of patients had impaired scores on at least one core skill preoperatively and postoperatively respectively. It was also found that the core skills measures were effective at discriminating amongst different neurological profiles. Specifically, patients with a left posterior tumour had significantly lower scores than other groups on measures of accessing semantic knowledge, lexical selection and phonological encoding, either pre or postoperatively, or both. Conversely, patients with a left frontal tumour had significantly lower scores on measures of articulatory motor planning and verb retrieval. Our Voxel-Lesion-Symptom-Mapping analysis corroborated these findings. Lesions within the left superior temporal lobe significantly predicted lows scores in accessing semantic knowledge, lexical selection and phonological encoding. Conversely, lesions within the left inferior, as well as the superior posterior frontal lobe, significantly predicted low scores on goal-driven response selection, articulatory-motor planning and verb retrieval. We conclude that a core skills approach may be a more effective means of assessing language in tumour populations than more conventional tools that emphasise overall task performance. Such derived measures are sensitive to impairments in this population, and are less likely to be confounded by nonlinguistic impairments that can impact significantly on overall task scores. They may also be useful in guiding postoperative rehabilitation. Further, the scores derived here are associated with quite specific neural substrates, making them potentially useful in guiding surgery and reducing postoperative linguistic deficits. Finally, we conclude that the investigation of tumour populations can also provide unique theoretical insights into language processing and its neural underpinnings in its own right.</p>